Bashar al-Assad, centre, with Hassan Turkmani, right, in 2005. Turkmani died in the bomb blast on 18 July along with Assef Shawkat, Assad’s brother-in-law, and Dawoud Rajha, defence minister. Photograph: Sana/AP

Syria's uprising entered uncharted territory after rebels fighting the regime of Bashar al-Assad killed three of his top security chiefs in a devastating bomb attack in the heart of Damascus – the single worst loss for the government in 16 months of increasingly bloody struggle.

Mass defections of soldiers and a rampage by pro-regime militiamen were reported in the capital amid a swirl of rumours, including one that Assad's wife, Asma, had fled to Russia and another that troops were being issued with gas masks, raising fears of the use of chemical weapons.

The president's whereabouts was also unclear, with one unconfirmed report that he had been wounded and left Damascus for Latakia on the coast.

Reports from Damascus on Wednesday described loud explosions, gunfire in the streets, attack helicopters firing and clouds of smoke over residential areas.

Earlier, Syrian state TV confirmed the deaths of Assef Shawkat, Assad's brother-in-law and the deputy head of the armed forces, and his closest security adviser, as well as Dawoud Rajha, the minister of defence and the regime's most senior Christian figure. Hassan Turkmani, his crisis management chief, was also killed.

Other leading figures, including the interior minister, Mohammad Shaar, and the intelligence chief, Hisham Bekhtyar, were wounded and being treated in the capital's al-Shami hospital. Uncertainty about the precise circumstances of the attack immediately gave rise to feverish speculation about possible internecine killings which the regime could blame on its enemies.

Explosions were also reported from the headquarters of the army's 4th Division in Damascus – the regime's elite unit commanded by Assad's brother, Maher.

Sergei Lavrov, Russia's foreign minister, said a "decisive battle" had begun in Syria. Lavrov also made it clear that Moscow would oppose a draft UN security council resolution threatening punishment if Assad did not implement the UN-backed peace plan promoted by Kofi Annan.

The US defence secretary, Leon Panetta, said Syria was now "rapidly spinning out of control".

In Syria, the Local Co-ordination Committees, an activist network, said 102 people had been killed in fighting across the country.

The morning attack on the headquarters of Syria's national security council in the al-Rawda area was the most audacious yet by anti-Assad rebels, who have been fighting sporadically in parts of the capital for the past four days. Syrian television said it was a suicide attack, and it was rumoured that the suspected killer may have been a bodyguard for Rajha or another member of Assad's inner circle. One pro-regime source in Damascus told the Guardian it was possible a bomb could have been planted on the premises.

The attack certainly appeared to be a deadly blow to the heart of the regime after two recent high-level defections – by a senior Republican Guard commander and Syria's ambassador to Iraq.

Syrian state television said foreign-backed "terrorists" had carried out the attack. The country's armed forces said in a statement that Syria was "determined to confront all forms of terrorism and chop off any hand that harms national security".

"The opposition has hit the jackpot," said Nadim Shehadi, a Middle East analyst at Chatham House in London. "The consequences are too big to digest. It may provoke more violence by the regime. Everyone is revising their calculations.

"People will be deciding whether to defect or not and the Russians will be wondering if they have backed the wrong horse," he said.

The attack was claimed by the Free Syrian Army, the main armed opposition group. "God willing, this is the beginning of the end of the regime," its commander, Riad al-Asaad, told AP in a telephone interview from Turkey. "Hopefully, Bashar will be next." An Islamist group called Liwa al-Islam also claimed responsibility.

Syrian state television, which was uncharacteristically quick to report the news, also said the military would call up its reserve forces on Thursday morning. Replacements for the three dead men were quickly announced.

General Fahd Jassem al-Freij, Rajha's replacement, denied reports on Arab satellite television channels about military defections in Idlib and Damascus and explosions at 4th Division HQ.

Rumours spread wildly in the hours after the incident, though much information was impossible to verify. According to one pro-government source, FSA rebels began moving around in pick-up trucks to demonstrate that they controlled parts of the city. Ba'ath party members had been executed by FSA men, the source said.

Damascus residents contacted by the Guardian said there had been no audible blast or visible damage at the site. Other Syrian sources suggested – without offering any evidence – that the three security chiefs might have been killed by the regime to forestall a possible coup or remove potential replacements for Assad.

"Either the generals were preparing a coup or if not there must be an intelligence operation here," said one Syrian analyst.

There were also widespread reports of defections in central Damascus as well as in the cities of Homs and Hama. Activists reported that several tanks had been abandoned near the centre of the capital and that several combat units had defected en masse. These reports could not be confirmed.

One activist, Omar al-Dimashki, said large numbers of troops and plainclothes police were deployed in the streets after the bombing, with snipers taking up positions on high buildings.

Shawkat, married to Assad's sister Bushra, was one of the most feared figures in the president's inner circle and had won the support of the clan's influential matriarch, Anisa. He was one of three central figures in the regime crackdown, along with Assad himself and his brother, Maher. As Syria's overall security chief, he had key input into all military and intelligence operations. He is known to have survived an attempt to poison him in late May when a cook contaminated food that had been prepared for him and key members of the national security ministry.

Abu Hamza, of the Free Syrian Army, told the Guardian at the time that rebel forces were trying to recruit aides of regime figures to carry out future attacks. "We have had some success with this," he said. "Some have been with us for a long time and have not yet been given orders to move."

Shawkat had also been a key point-man with Iran and with Hezbollah. Since the uprising started he had chaired key strategy meetings and had driven the regime's uncompromising and aggressive military response to the escalating dissent.

Rajha, a former general and an Orthodox Christian, was appointed defence minister last year in an apparent attempt by the Alawite-dominated regime to appoint a minority figure to a key job.

Prospects for any kind of negotiations between the government and rebels, always slim, have now all but disappeared.

Pro-regime Syrians appeared deeply shocked. "A lot of pro-Assad people are really panicking," said an opposition activist. "Now they sound really nervous."

Assad supporters admitted the attack was a serious blow. "This will not be the end of the regime in any way," said a member of Assad's Alawite community. "But it is serious and people are traumatised at the fact that the opposition managed to assassinate these people. But government supporters want the government to be firm and show it is still in control. The Syrian government is not usually impulsive."